Abstract：
The prostaglandin E2 (PGE2) receptor EP3 has been detected in the thick ascending limb (TAL) and the collecting duct of the kidney, where its actions are proposed to inhibit water reabsorption. However, EP3 is also expressed in other cell types, including vascular endothelial cells. The aim here was to determine the contribution of EP3 in renal water handling in male and female adult mice by phenotyping a novel mouse model with doxycycline-dependent deletion of EP3 throughout the kidney tubule (EP3-/- mice). RNAscope demonstrated that EP3 was highly expressed in the cortical and medullary TAL of adult mice. Compared to controls EP3 mRNA expression was reduced by >80% in whole kidney (RT-qPCR) and non-detectable (RNAscope) in renal tubules of EP3-/- mice. Under basal conditions, there were no significant differences in control and EP3-/- mice of both genders in food and water intake, bodyweight, urinary output or clinical biochemistries. No differences were detectable between genotypes in handling of an acute water load, or in their response to the vasopressin analogue dDAVP. No differences in water handling were observed when PGE2 production was enhanced using a 1% NaCl load. Expression of proteins involved in kidney water handling were not different between genotypes. This study demonstrates that renal tubular EP3 is not essential for body fluid homeostasis in males or females, even when PGE2 levels are high. The mouse model is a novel tool for examining the role of EP3 in kidney function independently of potential developmental abnormalities or systemic effects.
摘要：
前列腺素E2（PGE2）受体EP3已在肾脏的粗大上行肢体（TAL）和集合管中检测到，它的作用是为了抑制水的重吸收。然而,EP3也在其他细胞类型中表达，包括血管内皮细胞。这里的目的是通过在整个肾小管中具有强力霉素依赖性EP3缺失的新型小鼠模型（EP3-/-小鼠）的表型来确定EP3在雄性和雌性成年小鼠的肾脏水处理中的贡献。RNAscope证明EP3在成年小鼠的皮质和髓质TAL中高表达。与对照相比,EP3mRNA表达在EP3-/-小鼠的肾小管中减少>80%(RT-qPCR)和不可检测(RNAscope)。在基础条件下，两种性别的对照和EP3-/-小鼠在食物和水的摄入量上没有显着差异，体重,尿量或临床生化。在处理急性水负荷时，基因型之间没有检测到差异，或对加压素类似物dDAVP的反应。当使用1％NaCl负载提高PGE2产量时，未观察到水处理的差异。参与肾脏水处理的蛋白质的表达在基因型之间没有差异。这项研究表明，肾小管EP3对男性或女性的体液稳态不是必需的，即使PGE2水平很高。小鼠模型是一种新的工具，用于检查EP3在肾功能中的作用，而与潜在的发育异常或全身作用无关。
